Highly active antiretroviral therapy-induced regression of basal cell carcinomas in a patient with acquired immunodeficiency and Gorlin syndrome.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
M Helbert
Publications and source records attributed to M Helbert.
Optimising testing for phospholipid antibodies.
AIM: To compare anticardiolipin (ACL) and anti-beta2 glycoprotein 1 (beta2gp1) enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid syndrome (APS) and to incorporate these results into a meta-analysis of published data. METHOD: Three representative commercial ACL ELISAs and an in house beta2gp1 assay were optimised and then assessed on 124 sera from normal donors, patients with infection, or patients with APS. A Medline search was screened for papers meeting defined criteria to conduct a meta-analysis. The performance of the assays used in this study was included. RESULTS: A non-quantitative ACL assay performed at least as well as the anti-beta2gp1 assay in the diagnosis of APS. Meta-analysis confirmed that neither assay is perfect, although the anti-beta2gp1 assay had a higher specificity and lower sensitivity than the ACL assay. CONCLUSIONS: The pooled data suggest that the ACL assay is used to investigate thrombosis without overt underlying pathology and that the improved specificity of the anti-beta2gp1 assay is exploited where infection, connective tissue disease, or atheroma are present.
Antibodies, Anticardiolipin↗
A simple method for obtaining functionally and morphologically intact primary cultures of the medullary thick ascending limb of Henle's loop (MTAL) from rabbit kidneys.
We describe a simple method for obtaining functionally and morphologically intact primary cultures of cells from the medullary thick ascending limb of rabbit kidneys. After digesting dissected fragments of the inner stripe of the outer medulla with collagenase, a suspension of tubule fragments is obtained, the vast majority of which are medullary thick ascending limb (MTAL) segments. These are identified individually by their morphological appearance and large amounts are collected with a micropipette mounted on a micromanipulator. This ensures maximal homogeneity of the starting material. Monolayers of cells grow out of these MTAL segments after seeding them onto collagen-coated, permeable filter supports. During the week following confluence, the cultures exhibit an apical side-positive transepithelial potential difference. Electron microscopic examination shows a monolayer of polarised cells with characteristics of distal tubular cells. The primary cultures express Tamm-Horsfall protein at their apical surface. Additional evidence for their differentiation and polarisation is the net ammonium influx, which occurs at very high rates across the apical membrane and is much slower across the basolateral membrane, as judged by measurements of intracellular pH. Adenosine 3',5'-cyclic monophosphate (cAMP) production is stimulated by arginine-vasopressin, calcitonin or isoproterenol (all 1 micromol/l). Intracellular calcium signalling is observed after stimulation with 1 micromol/l adenosine, adenosine 5'-triphosphate (ATP) and bradykinin. In addition, we compared these characteristics with those of TALH-SVE cell monolayers, an established immortalised cell line of the same origin.
1-Methyl-3-isobutylxanthine↗
Benign monoclonal expansion of CD8+ lymphocytes in HIV infection.
BACKGROUND: A transient expansion of the CD8+ T cell pool normally occurs in the early phase of HIV infection. Persistent expansion of this pool is observed in two related settings: diffuse infiltrative lymphocytosis syndrome (DILS) and HIV associated CD8+ lymphocytosis syndrome. AIM: To investigate a group of HIV infected patients with CD8+ lymphocytosis syndrome with particular emphasis on whether monoclonality was present. METHODS: A group of 18 patients with HIV-1 infection and persistent circulating CD8+ lymphocytosis was compared with 21 HIV positive controls. Serum samples were tested for antinuclear antibodies, antibodies to extractable nuclear antigens, immunoglobulin levels, paraproteins, human T lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus, and cytomegalovirus serology. Lymphocyte phenotyping and HLA-DR typing was performed, and T cell receptor (TCR) gene rearrangement studies used to identify monoclonal populations of T cells. CD4+ and CD8+ subsets of peripheral blood lymphocytes were purified to determine whether CD8+ populations inhibited HIV replication in autologous CD4+ cells. RESULTS: A subgroup of patients with HIV-1 infection was found to have expanded populations of CD8+ T cell large granular lymphocytes persisting for 6 to 30 months. The consensus immunophenotype was CD4- CD8+ DRhigh CD11a+ CD11c+ CD16- CD28+/- CD56- CD57+, consistent with typical T cell large granular lymphocytes expressing cellular activation markers. Despite the finding of monoclonal TCR gene usage in five of 18 patients, there is evidence that the CD8+ expansions are reactive populations capable of mediating non-cytotoxic inhibition of HIV replication. CONCLUSIONS: A subgroup of HIV positive patients has CD8+ lymphocytosis, but despite the frequent occurrence of monoclonal TCR gene usage there is evidence that this represents an immune response to viral infection rather than a malignant disorder.
Adult↗
Monitoring patients with HIV disease.
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Antiviral Agents↗
Pathological investigation of deaths following surgery, anesthesia and medical procedures.
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Anaphylaxis↗
Temperature dependence of the ultraviolet-visible spectra of ionized and un-ionized forms of nitrophenol: consequence for the determination of enzymatic activities using nitrophenyl derivatives-A warning.
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Hydrogen-Ion Concentration↗
Drug-induced lupus nephritis in HIV infection.
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Adult↗
Paraproteins and monoclonal expansion of CD3+CD8+ CD56-CD57+ T lymphocytes in a patient with HIV infection.
An expansion of CD8+ lymphocytes associated with a monoclonal rearrangement of the T-cell receptor gamma locus was found in a woman with HIV-1 infection. A subpopulation of HIV-positive patients display an unusual response to HIV infection characterized by a persistent marked CD8+ lymphocytosis, the presence of which appears to be associated with an improved long-term prognosis. This condition is thought to represent a florid immune response to an ongoing viral infection which may be HIV itself, and suggests that monoclonal proliferation of CD8+ lymphocytes does not imply the presence of an underlying malignant process.
Antigens, CD↗
A simple flow cytometry assay using dihydrorhodamine for the measurement of the neutrophil respiratory burst in whole blood: comparison with the quantitative nitrobluetetrazolium test.
The neutrophil respiratory burst is essential for the host's ability to kill ingested microorganisms. Several flow cytometric assays have recently been developed to measure this process. These assays are largely unvalidated. In this study a whole blood flow cytometry assay using dihydrorhodamine 123 (DHR) as a substrate was compared with the quantitative nitrobluetetrazolium (NBT) test, an accepted measure of the earliest events in the respiratory burst. Because whole blood is used, the new assay is quicker and simpler than existing flow cytometry assays. Specimens as small as 0.1 ml can be used which makes the assay ideal for use in neonates and young children. There was a high degree of correlation between the DHR assay and the quantitative NBT test (r(s) = 0.76, P < 0.01). It is concluded that the whole blood DHR assay is an accurate and sensitive measure of the respiratory burst.
Adult↗
Analysis of human immunodeficiency virus type 1 (HIV-1) variants and levels of infection in dendritic and T cells from symptomatic HIV-1-infected patients.
Dendritic cells (DC) are required to initiate primary cellular immune responses. Human immunodeficiency virus type 1 (HIV-1) infection of DC may be central to transmission and persistence of virus and in the pathogenesis of AIDS. In symptomatic HIV-1-infected patients the proportion of DC in the mononuclear cell population was reduced. Provirus load in the T cells was 3-100 times higher than in DC and there was no correlation between the levels of infection in the two cell types. Phylogenetic analysis of amino acids in the V3 loop and flanking regions indicated intermingling of sequences and thus provides the first evidence for transfer of virus between DC and T cells in vivo. In one of three patients analysed there were significant differences in amino acid residues in the V3 region. This may reflect reduced interactions between DC and T cells in infected individuals and for the existence of variants with a stronger tropism for DC, which could play a role in transmission by initiating infection in mucosal DC.
Acquired Immunodeficiency Syndrome↗
Uveitis associated with rifabutin and macrolide therapy for Mycobacterium avium intracellulare infection in AIDS patients.
OBJECTIVE: Uveitis has been increasingly recognised as a side effect of rifabutin regimens in the prophylaxis and treatment of Mycobacterium avium intracellulare (MAI) infection. This study describes the clinical features and analyses the factors associated with rifabutin induced uveitis. DESIGN: Retrospective observational study. SETTING: Tertiary care institution, The Royal Hospitals NHS Trust, London. PATIENTS: 68 HIV seropositive individuals receiving rifabutin for prophylaxis or treatment of MAI infection. RESULTS: 11 episodes of uveitis occurred in 10 different individuals at a median of 62 days. The disease was bilateral in four and unilateral in the remainder. All subjects experienced ocular pain and photophobia and 9 individuals had a significant reduction in visual acuity. Uveitis was treated with mydriatics and topical steroids and resolved in all cases when rifabutin was stopped. The risk of uveitis was significantly increased with concurrent clarithromycin therapy, Odds Ratio 13.08, 95% Confidence Interval 1.98 to 83.12. CONCLUSION: Rifabutin can cause a reversible uveitis. This risk is increased with concurrent clarithromycin therapy. Adverse drug interactions can be an important cause of morbidity in patients with advanced HIV disease.
AIDS-Related Opportunistic Infections↗
The Concorde trial.
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Antigen-Presenting Cells↗
T-cell receptor variable gene products and early HIV-1 infection.
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Acquired Immunodeficiency Syndrome↗
Epstein-Barr virus associated oesophageal ulcers in AIDS.
Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration.
Acquired Immunodeficiency Syndrome↗
Mycobacterial infection in patients infected with the human immunodeficiency virus.
Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.
AIDS-Related Complex↗
Radiological features of AIDS related cholangitis.
Cryptosporidial infection is one of the recognised causes of diarrhoea in AIDS patients. It may also produce biliary tract disease. Fifteen out of 250 (6%) AIDS patients seen at our hospital had Cryptosporidial enteritis and five of the 15 (2% total) had clinical evidence of biliary tract disease. The radiological findings in these five patients are presented. Ultrasound examination of all five patients showed abnormalities in the biliary tree; five had dilatation and irregularity of the intra- and extrahepatic bile ducts with focal strictures, four had gall-bladder wall thickening, two had thickening of the common bile duct wall, two patients showed areas of increased reflectivity in the periductal regions of the liver and two had pancreatic duct dilatation. ERCP in one patient confirmed the ultrasound findings and Cryptosporidium oocytes were isolated from the collected bile. We conclude that Cryptosporidial infection in the biliary tree can produce distinctive appearances on ultrasound which may well obviate the need for more invasive investigations such as ERCP.
Acquired Immunodeficiency Syndrome↗